A major challenge for the BPRB is to begin to apply speci~c biomarkers in a rational way to permit more effective early detection approaches. Our laboratory resources will permit an intensive characterization of biomarkers and the biologic effects of intervention agents in a pilot study setting. Multiple markers have been implicated in the pathogenesis of human malignancies. Point mutations in the ras oncogene have been identi~ed in colorectal and lung carcinomas and have recently been identi~ed in shed epithelial cells found in stool specimens from patients with colorectal carcinomas. Alterations in carbohydrate antigen expression have also been found in malignancies and may be useful markers of neoplastic change. Shed epithelial cells in archived stool specimens from patients with documented colorectal cancer will be analyzed using polymerase chain reaction for oncogene mutations or activation, or changes in carbohydrate antigen expression. These ~ndings will be correlated with the markers present in the archived surgical material. Blocks from patients entered on a case-control study of colorectal cancer conducted at the National Naval Medical Center, Bethesda, Maryland have been obtained and are being analyzed for the presence of ras mutations and p53 expression. They will also be examined for carbohydrate antigen expression. If preliminary results are promising, additional specimens from patients entered on this study at Walter Reed Army Hospital and George Washington University Hospital, Washington, DC will also be obtained. Assays on stool specimens from control subjects will also be performed to assess the usefulness of these markers to discriminate patients with colorectal cancer from controls without cancer. The information obtained will be coupled with the previously collected epidemiologic data and Tumor Registry data for survival information to determine the potential usefulness for screening or prognostic purposes.